Studies on the role of Gata3 during development

Almost all cells in the living organism have identical genetic information, but each cell type expresses a limited number of genes. This phenomenon is regulated by specific proteins: transcription factors. These factors have the ability to recognize target sequences located at specific regulatory fragments located in or surrounding the gene (promoter, enhancer or LCR) and activate or repress gene transcription. Like many genes, the expression of transcription factors can also be restricted to particular cell types. This thesis is focused on the transcription factor GATA3, which is expressed in tissue specific manner during development. This chapter will introduce this factor and describes its sites of expression with the main focus on skin

Intergenerational differences as a challenge of leaders in the process of building commitment of employees in a public organization – an empirical research

Purpose: The article aims to show what challenges stem from employees' generational diversity and determine the level of engagement that leaders face in a public organization, using the example of the army. Design/Methodology/Approach: To answer the research problem, an analysis of the source literature (both Polish and foreign) together with a diagnostic survey was carried out with the use of questionnaire techniques on a sample of 158 soldiers – students and attendees of the courses conducted at the War Studies University in Warsaw. The results of the research were subjected to statistical analysis, which allowed to answer the research problem. Findings: The conducted research confirmed the existence of different thinking patterns of the representatives of generations X, Y, and Z, which constitutes a challenge for commanders in the army. The differences were noticed, especially about generation Z in the scope of interpersonal relations, teamwork, and work organization. Practical Implications: The results of the research are significant in the process of building the commitment of employees in public institutions. They reveal differences in the needs and expectations of a multigenerational team, which undoubtedly spur challenges for the leader to reconcile these needs and directly impact the level of commitment and, therefore, the ability to achieve the set goals. Originality/Value: The research provides theoretical assumptions and practical answers to encourage further research globally.peer-reviewe

Polimorfizm –A162G genu PON1 jako czynnik ryzyka rozwoju sporadycznej postaci stwardnienia bocznego zanikowego

Background and purpose: Sporadic amyotrophic lateral sclerosis (sALS) is a devastating neurodegenerative disease, which results from complex genetic and environmental interactions. Recent studies have reported an association between several polymorphisms of the PON1 and PON2 genes and risk of sALS. The aim of the present study was to identify an association between the –A162G polymorphism of the promoter region of the human PON1 gene and the risk of sALS in a Polish population. Material and methods: We included 259 patients with a diagnosis of definite or probable sALS (76 bulbar onset, 183 limb onset) and 694 healthy controls matched for age and sex. The diagnosis of ALS was established according to El Escorial criteria. The polymorphism was studied by Single Nucleotide Polymorphism Real-Time Polymerase Chain Reaction analysis. Results: No overall difference in the PON1 –A162G geno - type and allele distribution was seen between cases and controls (all p > 0.05). There was, however, a difference in the A allele frequency when the bulbar onset group was compared to the controls (p = 0.03), but this significance disappeared after the Bonferroni correction. Conclusions: The results did not show that the –A162G polymorphism of the PON1 gene is a risk factor of sALS in a Polish population; it may affect, however, bulbar onset of the disease

Transcriptome and phenotypic analysis reveals Gata3-dependent signalling pathways in murine hair follicles

Abstract The transcription factor Gata3 is crucially involved in epidermis and hair follicle differentiation. Yet, little is known about how Gata3 co-ordinates stem cell lineage determination in skin, what pathways are involved and how Gata3 differentially regulates distinct cell populations within the hair follicle. Here, we describe a conditional Gata3-/- mouse (K14-Gata3-/-) in which Gata3 is specifically deleted in epidermis and hair follicles. K14-Gata3-/- mice show aberrant postnatal growth and development, delayed hair growth and maintenance, abnormal hair follicle organization and irregular pigmentation. After the first hair cycle, the germinative layer surrounding the dermal papilla was not restored; instead, proliferation was pronounced in basal epidermal cells. Transcriptome analysis of laser-dissected K14-Gata3-/- hair follicles revealed mitosis, epithelial differentiation and the Notch, Wnt and BMP signaling pathways to be significantly overrepresented. Elucidation of these pathways at the RNA and protein levels and physiologic endpoints suggests that Gata3 integrates diverse signaling networks to regulate the balance between hair follicle and epidermal cell fates

Polimorfizm –A162G genu PON1 jako czynnik ryzyka rozwoju sporadycznej postaci stwardnienia bocznego zanikowego

Background and purpose Sporadic amyotrophic lateral sclerosis (sALS) is a devastating neurodegenerative disease, which results from complex genetic and environmental interactions. Recent studies have reported an association between several polymorphisms of the PON1 and PON2 genes and risk of sALS. The aim of the present study was to identify an association between the – A162G polymorphism of the promoter region of the human PON1 gene and the risk of sALS in a Polish population. Material and methods We included 259 patients with a diagnosis of definite or probable sALS (76 bulbar onset, 183 limb onset) and 694 healthy controls matched for age and sex. The diagnosis of ALS was established according to El Escorial criteria. The polymorphism was studied by Single Nucleotide Polymorphism Real-Time Polymerase Chain Reaction analysis. Results No overall difference in the PONI – A162G genotype and allele distribution was seen between cases and controls (all p > 0.05). There was, however, a difference in the A allele frequency when the bulbar onset group was compared to the controls (p = 0.03), but this significance disappeared after the Bonferroni correction. Conclusions The results did not show that the – A162G polymorphism of the PON1 gene is a risk factor of sALS in a Polish population; it may affect, however, bulbar onset of the disease.Wstęp i cel pracy Sporadyczna postać stwardnienia bocznego zanikowego (sSLA) jest chorobą zwyrodnieniową układu nerwowego, w której etiopatogenezie kluczową rolę odgrywają interakcje między czynnikami genetycznymi i środowiskowymi. Dotychczasowe badania wskazują na istnienie zależności między polimorfizmami genów PON1 i PON2 a ryzykiem wystąpienia sSLA. Celem pracy było zbadanie, czy istnieje związek między polimorfizmem – A162G miejsca promotorowego genu PON1 a ryzykiem wystąpienia sSLA w populacji polskiej. Materiał i metody Badanie przeprowadzono u 259 chorych, uktórych zgodnie z kryteriami El Escorial rozpoznano pewne lub prawdopodobne SLA (76 osób z postacią opuszkową, 183 osoby z postacią kończynową) oraz u 694 zdrowych ochotników, stanowiących grupę kontrolną dobraną pod względem wieku i płci. Polimorfizm genu PON1 był badany za pomocą reakcji łańcuchowej polimerazy DNA z analizą ilości produktu w czasie rzeczywistym. Wyniki Nie stwierdzono istotnych statystycznie różnic w rozkładzie genotypów i alleli genu PON1 między grupą chorych a grupą kontrolną (p > 0,05). Stwierdzono natomiast różnice w częstości występowania allela A między grupą chorych z postacią opuszkową w porównaniu z grupą kontrolną (p = 0,03), jednak po korekcie Bonferroniego wynik ten nie był już istotny statystycznie. Wnioski Wyniki naszego badania nie wykazały, aby polimorfizm – A162G genu PON1 był czynnikiem ryzyka sSLA w populacji polskiej, jednak sugerują, że może mieć znaczenie dla wystąpienia postaci opuszkowej tej choroby

Identification of Multiple Subsets of Ventral Interneurons and Differential Distribution along the Rostrocaudal Axis of the Developing Spinal Cord

The spinal cord contains neuronal circuits termed Central Pattern Generators (CPGs) that coordinate rhythmic motor activities. CPG circuits consist of motor neurons and multiple interneuron cell types, many of which are derived from four distinct cardinal classes of ventral interneurons, called V0, V1, V2 and V3. While significant progress has been made on elucidating the molecular and genetic mechanisms that control ventral interneuron differentiation, little is known about their distribution along the antero-posterior axis of the spinal cord and their diversification. Here, we report that V0, V1 and V2 interneurons exhibit distinct organizational patterns at brachial, thoracic and lumbar levels of the developing spinal cord. In addition, we demonstrate that each cardinal class of ventral interneurons can be subdivided into several subsets according to the combinatorial expression of different sets of transcription factors, and that these subsets are differentially distributed along the rostrocaudal axis of the spinal cord. This comprehensive molecular profiling of ventral interneurons provides an important resource for investigating neuronal diversification in the developing spinal cord and for understanding the contribution of specific interneuron subsets on CPG circuits and motor control

Expression of prophage-encoded endolysins contributes to autolysis of Lactococcus lactis

Analysis of autolysis of derivatives of Lactococcus lactis subsp. cremoris MG1363 and subsp. lactis IL1403, both lacking the major autolysin AcmA, showed that L. lactis IL1403 still lysed during growth while L. lactis MG1363 did not. Zymographic analysis revealed that a peptidoglycan hydrolase activity of around 30 kDa is present in cell extracts of L. lactis IL1403 that could not be detected in strain MG1363. A comparison of all genes encoding putative peptidoglycan hydrolases of IL1403 and MG1363 led to the assumption that one or more of the 99 % homologous 27.9-kDa endolysins encoded by the prophages bIL285, bIL286 and bIL309 could account for the autolysis phenotype of IL1403. Induced expression of the endolysins from bIL285, bIL286 or bIL309 in L. lactis MG1363 resulted in detectable lysis or lytic activity. Prophage deletion and insertion derivatives of L. lactis IL1403 had a reduced cell lysis phenotype. RT-qPCR and zymogram analysis showed that each of these strains still expressed one or more of the three phage lysins. A homologous gene and an endolysin activity were also identified in the natural starter culture L. lactis subsp. cremoris strains E8, Wg2 and HP, and the lytic activity could be detected under growth conditions that were identical as those used for IL1403. The results presented here show that these endolysins of L. lactis are expressed during normal growth and contribute to autolysis without production of (lytic) phages. Screening for natural strains expressing homologous endolysins could help in the selection of strains with enhanced autolysis and, thus, cheese ripening properties

Canonical Wnt signaling negatively modulates regulatory T cell function

Foxp3 is crucial for both the development and function of regulatory T (Treg) cells; however, the posttranslational mechanisms regulating Foxp3 transcriptional output remain poorly defined. Here, we demonstrate that Tcell factor 1 (TCF1) and Foxp3 associates in Treg cells and that active Wnt signaling disrupts Foxp3 transcriptional activity. A global chromatin immunoprecipitation sequencing comparison in Treg cells revealed considerable overlap between Foxp3 and Wnt target genes. The activation of Wnt signaling reduced Treg-mediated suppression both invitro and invivo, whereas disruption of Wnt signaling in Treg cells enhanced their suppressive capacity. The activation of effector Tcells increased Wnt3a production, and Wnt3a levels were found to be greatly increased in mononuclear cells isolated from synovial fluid versus peripheral blood of arthritis patients. We propose a model in which Wnt produced under inflammatory conditions represses Treg cell function, allowing a productive immune response, but, if uncontrolled, could lead to the development of autoimmunity

Occurrence of Dirofilaria repens in wild carnivores in Poland.

Dirofilaria repens is an expanding vector-borne zoonotic parasite of canines and other carnivores. Sub-clinically infected dogs constitute the most important reservoir of the parasite and the source of infection for its mosquito vectors. However, occurrence of D. repens infection in wild animals may contribute to the transmission of the parasite to humans and may explain the endemicity of filariae in newly invaded regions. The aim of the current study was to determine the occurrence of D. repens in 511 blood and spleen samples from seven species of wild carnivores (wolves, red foxes, Eurasian badgers, raccoons, raccoon dogs, stone martens, and pine martens) from different regions of Poland by means of a PCR protocol targeting the 12S rDNA gene. Dirofilaria repens–positive hosts were identified in seven of fourteen voivodeships in four of the seven regions of Poland: Masovia, Lesser Poland, Pomerania and Warmia-Masuria. The highest prevalence was found in Masovia region (8%), coinciding with the highest previously recorded prevalence in dogs in Central Poland. The DNA of Dirofilaria was detected in 16 samples of three species (total prevalence 3.13%). A low and similar percentage of positive samples (1.9%, 4.2% and 4.8%) was recorded among badgers, red foxes, and wolves, respectively. Dirofilaria repens–positive hosts were identified in seven of fourteen voivodships. Based on detection in different voivodeships, D. repens–positive animals were recorded in four out of the seven regions of Poland: in Masovia, Lesser Poland, Pomerania, and Warmia-Masuria. The highest prevalence of filariae was found in Masovia region (8%), reflecting the highest previously recorded prevalence in dogs (12–50%) in Central Poland. In summary, we conducted the first comprehensive study on the epidemiology of D. repens in seven species of wild hosts in all seven regions of Poland and identified the first case of D. repens infection in Eurasian badgers in Poland and the second in Europe

Endogenous WNT signals mediate BMP-induced and spontaneous differentiation of epiblast stem cells and human embryonic stem cells

Therapeutic application of human embryonic stem cells (hESCs) requires precise control over their differentiation. However, spontaneous differentiation is prevalent, and growth factors induce multiple cell types; e.g., the mesoderm inducer BMP4 generates both mesoderm and trophoblast. Here we identify endogenous WNT signals as BMP targets that are required and sufficient for mesoderm induction, while trophoblast induction is WNT independent, enabling the exclusive differentiation toward either lineage. Furthermore, endogenous WNT signals induce loss of pluripotency in hESCs and their murine counterparts, epiblast stem cells (EpiSCs). WNT inhibition obviates the need to manually remove differentiated cells to maintain cultures and improves the efficiency of directed differentiation. In EpiSCs, WNT inhibition stabilizes a pregastrula epiblast state with novel characteristics, including the ability to contribute to blastocyst chimeras. Our findings show that endogenous WNT signals function as hidden mediators of growth factor-induced differentiation and play critical roles in the self-renewal of hESCs and EpiSCs